Genetic epidemiology

In this chapter, we describe both the historical and contemporary terminologies that reflect the evolving field of genetic epidemiology. We discuss the conduct of family-based studies to identify high-penetrance disease genes, along with traditional genetic analyses of human pedigrees to assess Mendelian transmission (segregation analysis) or to locate causal genes (linkage analysis/gene mapping). We also describe epidemiologic approaches used to study gene-disease associations (including genome-wide association studies) plus gene-gene and gene-environment interactions. We review analytic and methodologic issues applicable to each of these studies and emerging, nontraditional epidemiologic methods that can be used as an adjunct to traditional approaches, particularly for the simultaneous study of hundreds of thousands of data points per person. We further discuss the challenging nature of analysis, synthesis, and dissemination of these genetic data, and the value of systematic reviews, meta-analyses and consortia in evaluating large bodies of scientific evidence. Finally, we describe the need for follow-up of these results to identify causal variants and the need for translational research efforts to apply these gene discoveries to personalized medicine, such as evaluation of genetic testing in clinical practice (in terms of analytic validity, clinical validity, clinical utility), and to population health including determining the disease risk and burden in populations (e.g., absolute and attributable risks). We also consider the ethical, legal, and social implications of these discoveries.